Mosunetuzumab for Early Relapse of Follicular Lymphoma in the Nordic Countries

NCT05849857 | Recruiting Phase 2

• 3 other identifiers: EU CT NO: 2022-500100-21-01NLG-FL6ML43841
• Study Type: interventional
• Target: 80
• Locations: 2 countries
• Sites: 3

Brief Summary

In this clinical trial adult patients diagnosed with follicular lymphoma and relapse or progression of disease within 24 months of starting first line treatment will be treated with mosunetuzumab. This is a bispecific antibody, a new type of immunotherapy that redirects the bodies own immune cells (T-cells) to attack and kill the lymphoma cells. The main question the trial aims to answer is if mosunetuzumab works better than standard treatments in this sub-group of patients. Patients will receive mosunetuzumab as injections in the abdominal subcutaneous fat once a week for the three first doses, then every third week 7 times. If all signs of disease are gone as evaluated by PET-CT images, the treatment is stopped. If signs of disease remain on PET-CT images, the patients can receive treatment every third week for up to a total of one year. After the end of treatment, patients are followed two years in the trial for signs of progression or relapse.

Conditions

Lymphoma, Follicular

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression free survival

  From the date of starting treatment to the date of first documented progression of disease or death of any cause, whichever came first. Patients will be observed for a minimum of 2 years and a maximum of 4 years for the primary outcome

Secondary Outcomes (7)

• ORR

  At the end of 8 cycles (each cycle is 21 days)

• CRR

  At the end of 8 cycles (each cycle is 21 days)

• DOR

  From the date of first documented response to the date of first documented disease progression or death from any cause. Patients will be observed for a minimum of 2.5 years and a maximum of 5 years for the DOR

• TTNT

  From the date of starting study treatment to the date of starting 3rd line therapy due to progression of disease or to death of any cause, whichever came first. Patients will be observed for a minimum of 2.5 years and a maximum of 5 years for TTNT.

• OS

  From the date of inclusion to the date of death of any cause. Patients will be observed for a minimum of 2.5 years and a maximum of 5 years for OS.

Study Arms (1)

Subcutaneous mosunetuzumab

EXPERIMENTAL

The duration of each treatment cycle is 21 days. Cycle 1 Day 1: 5 mg Mosunetuzumab SC Cycle 1 Day 8: 45 mg Mosunetuzumab SC Cycle 1 Day 15: 45 mg Mosunetuzumab SC Cycle 2-8 Day 1: 45 mg Mosunetuzumab SC Patients in complete remission after 8 cycles enter follow-up. Patients with stable disease or partial remission can receive up to a total of 17 cycles: Cycle 9-17 Day 1: 45 mg Mosunetuzumab SC

Drug: Mosunetuzumab

Interventions

Mosunetuzumab DRUG

Mosunetuzumab is administered as a subcutaneous injection. The first dose is 5 mg in 0,5 mL volume, subsequent doses are 45 mg in 1,0 mL volume.

Also known as: Dexamethasone

Subcutaneous mosunetuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent according to ICH-GCP guidelines.
• Age ≥ 18 years.
• Follicular lymphoma grade 1-3a with a current relapse or progression within 24 months of starting 1st line treatment or refractory to 1st line treatment (POD24), more specifically:
• Documented current relapse or progression of FL within 24 months of starting first line treatment containing a monospecific anti-CD20 antibody (such as rituximab or obinutuzumab with or without chemotherapy, small molecular inhibitors or immunomodulating agents such as lenalidomide).
• Current lack of response/refractoriness to first line treatment, i.e., no objective response or documented progression within 6 months following at least four cycles of monotherapy with a monospecific anti-CD20 antibody (such as rituximab 375mg/m2 iv or 1400 mg SC or equal) or following at least three cycles of a monospecific anti CD20 antibody combined with chemotherapy, small molecular inhibitors or immunomodulating agents such as lenalidomide.
• Received one prior treatment line of systemic therapy.
• Patients may have had a period of watch and wait before the initiation of first line treatment.
• Patients may have received localized radiotherapy previously.
• At least one two-dimensionally measurable lesion with a longest diameter \>15mm.
• WHO performance status 0-2. Patients with reduced WHO performance status (\> 2) can be considered if reduction in performance is caused by the lymphoma as determined by the investigator.

You may not qualify if:

• Received 2 or more previous treatment lines.
• Grade 3b FL.
• CD20-negative lymphoma.
• CNS involvement (current or previous).
• Impaired bone marrow function (neutrophils \< 1.0 x 109/L or platelets \< 50 x 109/L) unless due to lymphoma involvement.
• Severe cardiac disease: impaired cardiac function (NYHA class III or IV), myocardial infarction within the last 6 months, unstable arrythmias and/or unstable angina pectoris.
• Impaired liver function not caused by lymphoma, defined as serum total bilirubin ≥ 1.5 x ULN (unless elevated due to Gilbert's syndrome) or serum ALT and AST \> 3 x ULN.
• Impaired renal function not caused by lymphoma, defined as calculated creatinine clearance ≤ 40 ml/minute.
• Other major organ dysfunction not caused by lymphoma.
• Known history of drug induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension.
• Active severe infection.
• Hepatitis B (HBV) or hepatitis C (HCV) infection: Subjects with a previous hepatitis B infection will be eligible if they are negative for HBV-DNA; these subjects must be given prophylactic antiviral therapy. Subjects with a previous HCV infection will be eligible if they are negative for HCV-RNA.
• Known or suspected chronic active Epstein-Barr virus (EBV) infection.
• Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within two weeks prior to the first dose of mosunetuzumab.
• Administration of live vaccines within four weeks of the first dose of mosunetuzumab or anticipation that live vaccine will be required during the study.

Sponsors & Collaborators

• Oslo University Hospital: lead
• Hoffmann-La Roche: collaborator
• Aarhus University Hospital: collaborator

Study Sites (3)

Helsinki University Hospital

Helsinki, Finland

RECRUITING

Oslo University Hospital

Oslo, 0424, Norway

RECRUITING

St. Olavs hospital

Trondheim, Norway

RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Marianne Brodtkorb, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Louise Krüger Hansen

CONTACT

+45 24782645; louise.kruger.hansen@rm.dk

Lise Nylund Torpen

CONTACT

+ 47 90864581; linyto@ous-hf.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior consultant, Department of Oncology, Principal Investigator, M.D., Ph.D.

Model Details: Phase II, one arm, open label clinical trial of subcutaneous mosunetuzumab mono-therapy

Study Record Dates

• First Submitted: March 22, 2023
• First Posted: May 9, 2023
• Study Start: September 11, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: November 1, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

NO (2); FI (1)